Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP

Nat Struct Biol. 1998 Sep;5(9):803-11. doi: 10.1038/1843.


N-ethylmaleimide-sensitive factor (NSF) is a hexameric ATPase which primes and/or dissociates SNARE complexes involved in intracellular fusion events. Each NSF protomer contains three domains: an N-terminal domain required for SNARE binding and two ATPase domains, termed D1 and D2, with D2 being required for oligomerization. We have determined the 1.9 A crystal structure of the D2 domain of NSF complexed with ATP using multi-wavelength anomalous dispersion phasing. D2 consists of a nucleotide binding subdomain with a Rossmann fold and a C-terminal subdomain, which is structurally unique among nucleotide binding proteins. There are interactions between the ATP moiety and both the neighboring D2 protomer and the C-terminal subdomain that may be important for ATP-dependent oligomerization. Of particular importance are three well-ordered and conserved lysine residues that form ionic interactions with the beta- and gamma-phosphates, one of which likely contributes to the low hydrolytic activity of D2.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cricetinae
  • Crystallography, X-Ray
  • DNA Primers / genetics
  • Humans
  • Membrane Proteins / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • N-Ethylmaleimide-Sensitive Proteins
  • Polymerase Chain Reaction
  • Protein Conformation
  • SNARE Proteins
  • Sequence Homology, Amino Acid
  • Static Electricity
  • Vesicular Transport Proteins*


  • Carrier Proteins
  • DNA Primers
  • Membrane Proteins
  • SNARE Proteins
  • Vesicular Transport Proteins
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • N-Ethylmaleimide-Sensitive Proteins
  • Nsf protein, mouse

Associated data

  • PDB/1NSF